17-63832948-C-G

Position:

• chr17-63832948-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001098426.2(SMARCD2):​c.1586G>C​(p.Arg529Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R529H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCD2 NM_001098426.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94

Genes affected

SMARCD2 (HGNC:11107): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCD2	NM_001098426.2	c.1586G>C	p.Arg529Pro	missense_variant	13/13	ENST00000448276.7
SMARCD2	NM_001330440.2	c.1442G>C	p.Arg481Pro	missense_variant	13/13
SMARCD2	NM_001330439.1	c.1361G>C	p.Arg454Pro	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCD2	ENST00000448276.7	c.1586G>C	p.Arg529Pro	missense_variant	13/13	1	NM_001098426.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 21, 2022

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 529 of the SMARCD2 protein (p.Arg529Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCD2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	29
DANN	Benign	0.91
DEOGEN2	Benign	0.14	T;T;.;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Uncertain	-0.14	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.82	D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.42
MutPred		0.65		.;Loss of MoRF binding (P = 0.0078);.;.;
MVP		0.56
MPC		1.5
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.85
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-61910308;